The weight of evidences, which let to doubt on the efficacy and safety of ferrous sulfate oral administration, has stimulated the research of more effective approaches to prevent ID and toxicity associated with iron overload. The treatment of ID and IDA during pregnancy should be entirely reconsidered taking into account not only the enhanced blood volume and development of fetal-placenta unit, but also other factors, as IL-6, which, inducing hepcidin up-regulation and ferroportin down-regulation, can play a pivotal role in iron homeostasis disorders.